The present invention is in the field of enzyme proteins that are related to the helicase subfamily, recombinant DNA molecules, and protein production. The present invention specifically provides novel peptides and proteins that effect protein phosphorylation and nucleic acid molecules encoding such peptide and protein molecules, all of which are useful in the development of human therapeutics and diagnostic compositions and methods.
Many human enzymes serve as targets for the action of pharmaceutically active compounds. Several classes of human enzymes that serve as such targets include helicase, steroid esterase and sulfatase, convertase, synthase, dehydrogenase, monoxygenase, transferase, kinase, glutanase, decarboxylase, isomerase and reductase. It is therefore important in developing new pharmaceutical compounds to identify target enzyme proteins that can be put into high-throughput screening formats. The present invention advances the state of the art by providing novel human drug target enzymes related to the helicase subfamily.
Helicases
The novel human enzyme, and encoding gene is similar to the RNA helicase HDB protein, also known as the DICE1 (xe2x80x9cdeleted in cancer 1xe2x80x9d) protein.
DICE1 is a candidate tumor suppressor gene, particularly in non-small cell lung carcinomas, and carcinomas of the head and neck, breast, ovary, prostate, as well as other carcinomas. DICE1 is expressed in a wide variety of adult and fetal tissues and is highly conserved in evolution, it""s expression is down-regulated or abolished in carcinomas, and it is located in a chromosomal region associated with tumor suppression and loss of heterozygosity. DICE1 shares 92.9% amino acid sequence identity with the carboxy-terminal half of mouse EGF repeat transmembrane protein DB-1, a protein that limits mitogenic response to insulin-like growth factor 1 and likely plays a role in anchorage-dependent growth (Wieland et al., Oncogene 18: 4530-4537, 1999).
Therefore, novel human helicase proteins/genes may be particularly useful in the diagnosis, prevention, and/or treatment of carcinomas.
Enzyme proteins, particularly members of the helicase subfamily, are a major target for drug action and development. Accordingly, it is valuable to the field of pharmaceutical development to identify and characterize previously unknown members of this subfamily of enzyme proteins. The present invention advances the state of the art by providing previously unidentified human enzyme proteins, and the polynucleotides encoding them, that have homology to members of the helicase subfamily. These novel compositions are useful in the diagnosis, prevention and treatment of biological processes associated with human diseases.
The present invention is based in part on the identification of amino acid sequences of human enzyme peptides and proteins that are related to the helicase subfamily, as well as allelic variants and other mammalian orthologs thereof. These unique peptide sequences, and nucleic acid sequences that encode these peptides, can be used as models for the development of human therapeutic targets, aid in the identification of therapeutic proteins, and serve as targets for the development of human therapeutic agents that modulate enzyme activity in cells and tissues that express the enzyme. Experimental data as provided in FIG. 1 indicates expression in humans in the fetal liver/spleen, breast, hypothalamus, ovarian tumors, lung fibroblasts, and brain.